Influences of Sacubitril/Valsartan (ENTRESTO®) on centrally generated sympathetic activity in heart failure patients

Phase 1

• Conditions: Chronic heart failure with reduced left ventricular ejection fraction (NYHA II-III); MedDRA version: 20.0Level: LLTClassification code 10078289Term: Heart failure with reduced ejection fractionSystem Organ Class: 100000004849; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2017-000394-36-DE
• Lead Sponsor: Hannover Medical School

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-08-02
• Last Update Posted: 9 May 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

1. Women or men at the age = 18 years, = 80 years and able to give written informed consent
2. Heart failure NYHA class II-III
3. Ejection fraction of 40 % or less (any measurement made within the past 6 month using echocardiography, MUGA, CT scanning, MRT or ventricular angiography is acceptable, provided no subsequent measurement above 40%)
4. ACE inhibitor or ARB at a stable dose of at least enalapril 10 mg/d or equivalent for at least 4 weeks before visit 1 (screening)
5. Stable dose of a beta-blocker for at least 4 weeks before visit 1 unless contraindicated or not tolerated
6. Patient has to be in sinus rhythm
7. Patients capable of understanding the investigational nature, potential risks and benefits of the clinical trial
8. Women without childbearing potential defined by:
• at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy or
• hysterectomy or uterine agenesis or
• = 50 years and in postmenopausal state = 1 year or
• < 50 years and in postmenopausal state = 1 year with serum FSH > 40 IU/l and serum estrogen< 30 ng/l or a negative estrogen test
OR
Women of childbearing potential with a negative urine ß-HCG pregnancy test at screening who agree to meet one of the following criteria from the time of screening, during the study and for a period of 7 days following the last administration of study medication:
• correct use of at least an acceptable effective contraceptive measure. The following are deemed acceptable in this study: hormonal contraceptives (combined oral contraceptives and estrogen-free pills with desogestrel, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release), intrauterine device (IUS)
• true abstinence (periodic abstinence and withdrawal are not acceptable methods of contraception)
• sexual relationship only with female partners and/or sterile male partners
OR
Male
9. Signed written informed consent and willingness to comply with treatment and follow- up procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 14
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 21

Exclusion Criteria

1. History of hypersensitivity or allergy to any of the study drugs, drugs of similar chemical classes, ACE inhibitors (ACE-Is), ARBs, or neprilysin inhibitors, as well as known or suspected contraindications to the study drugs
2. Known history of angioedema
3. Recent acute decompensated heart failure within 2 months before screening (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy)
4. Symptomatic hypotension and/or office systolic BP <110 mmHg at visit 1
5. Combined intake of an ACE inhibitor and ARB over the last 4 weeks before visit 1
6. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² as measured by the simplified MDRD forumla
7. Concomitant medication with Aliskiren in patients with Diabetes or patients with eGFR < 60 mL/min/1.73 m² as measured by the simplified MDRD forumla
8. Serum potassium >5.2 mmol/L at Visit 1 (screening)
9. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid, or other major cardiovascular surgery, PCI, or carotid angioplasty within the 3 months before screening
10. History of heart transplant or on a transplant list or with LV assistance device
11. History of severe pulmonary disease
12. Documented untreated ventricular arrhythmia with syncopal episodes within the 3 months prior to Visit 1
13. Presence of hemodynamically significant mitral and/or aortic valve disease/ left ventricular outflow tract obstruction, except mitral regurgitation secondary to LV dilatation
14. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs
15. Evidence of hepatic disease as determined by any one of the following: aspartate aminotransferase or alanine aminotransferase values exceeding 2× upper limit of normal at Visit 1, history of hepatic encephalopathy, history of esophageal varices, or history of porto-caval shunt
16. Contraindications precluding microneurography measurements, such as relevant peripheral neuropathy as judged by the investigator
17. Pregnancy or lactation period
18. Current participation in any other clinical trial or participation in another clinical trial within 30 days before screening
19. Known or suspected hypersensitivity to any of the active substances or any excipients of the investigational medicinal products
20. Vulnerable subjects (i.e. persons under any administrative or legal supervision or persons kept in detention)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified